CFS may be associated with the disruption of several physiological processes such as exercise capacity, sleep, cognition and immune function. Most investigations of CFS have used a case-control design with patients recruited from referral centers and controls often matched only of age and sex. Thus, these disorders have not adjusted for genetic and environmental influences. The study of monozygotic (MZ) twins discordant for CFS (i.e., one has CFS, one doesn't) adjusts for genetic variability and common familial exposures. We have constructed a large registry of twins in which at least one member has CFS or a similar illness. All Twin Registry members complete a comprehensive Registry Booklet and a structured psychiatric interview. Using this information and medical records, 21 pairs of CFS discordant twins (CFS-HY) have been selected for a 6-day evaluation that includes polysomnography, exercise capacity testing, neuropsychological assessment, SPECT imaging, a psychiatric and life events interview, tests of viral replication and the immune system (Phase 1). Data from the 17 CFS-HY twin pairs who have completed this evaluation demonstrate remarkably disrupted sleep, poor performance on the several cognitive tests and severely impaired exercise capacity in both twins, as well as intriguing differences in immune function and perceptual style. In Phase 2, the twins will return to Seattle 24-30 months after Phase 1 for further intensive study that will include polysomnography, neuropsychological testing, exercise capacity testing and measurement and measurement of immune function and perception. We will also examine 10 pairs of twins in which both members are health (HY-HY) to clarify the interpretation of the abnormalities documented in the healthy member of the CFS-HY pairs. Our aims are to confirm the Phase 1 results and to assess their stability and reproducibility; 2) improve the interpretation of Phase 1 abnormalities by expanded data collection using challenge studies and other approaches to bring out differences between the CFS-HY twins; 3) compare the results in the CFS-HY pairs with those obtained from HY- HY twins. If abnormalities are not found in HY-HY twins then the impairments in exercise, cognition and sleep may represent predisposing factors that place the healthy member of the CFS-HY pair at risk for illness; 4) establish the extent to which alterations in perception account for dysfunction in CFS.